The Secret to Fast-Acting Antidepressants

Scientists have uncovered the antidepressant mechanism behind ketamine — an anesthetic, a recreational dance-party drug, and, as it turns out, an unusually fast-acting mood booster. The scientists hope that their finding will lead to the development of other, new drugs that can help patients recover from depression faster.

Major depressive disorder affects some 17% of Americans, according to the paper, due to be published tomorrow in Science. But most antidepressant drugs take weeks or months before patients see results. Ketamine is an exception. That’s because — the researchers have discovered, in rats — ketamine rapidly activates something called the mammalian target of rapamycin (mTOR), which then increases levels of the synaptic proteins that are ordinarily diminished in the prefrontal cortex of depressed patients. The results, the authors write, “indicate that ketamine induction of synapse-associated protein synthesis provides a mechanism for rapid reversal of stress- and/or depression-mediated deficits” in the prefrontal cortex.

It’s possible that other drugs targeting the same pathway, mTOR, would have similarly rapid antidepressant effects — a big improvement over today’s drugs. Of course, however, so far this test has only been run in rats. It’s unclear exactly whether newly developed drugs for humans might see the same results — and ketamine itself is a controlled substance. It’s a Schedule III drug under federal law.